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目的研究多发性硬化(MS)患者所具有的与人类疱疹病毒6型(HHV-6)病毒/人类疱疹病毒4型病毒(EBV)和髓鞘碱性蛋白(MBP)发生交叉反应的CD4+/CD8+T细胞,以及MS患者血清和脑脊液中MBP和抗病毒抗体表达状况,探讨MS发病与HHV-6/EBV感染的关系。方法通过氚标记胸腺嘧啶核苷(3H-TdR)掺入实验分析HHV-6/EBV病毒肽和MBP肽段诱导的MS患者CD4+和CD8+T细胞的应答反应,以高灵敏ELISA试剂盒检测MS患者脑脊液和血清中抗HHV-6/EBV抗体水平,并以引物序列特异的PCR(SSP-PCR)技术分析MS患者HLA-Ⅱ类分子DRB1的表达格局。结果 (1)MS患者HLA-Ⅱ类分子DRB1*04基因(41.7%)与健康对照组(18.7%)相比具有较高的检出率,但差异无统计学意义(P>0.05)。(2)MS患者血清中存在高水平抗HHV-6抗体,同时亦可检测出抗EBV壳蛋白抗原(VCA)IgG抗体和EBV核抗原-1(EBNA-1)的IgG抗体。(3)3H-TdR掺入实验结果表明,MS患者的CD4+T细胞或CD8+T细胞对自身MBP肽段及合成的HHV-6/EBV肽段的诱导作用均存在交叉反应。结论 HHV-6/EBV与MS患者MBP自身抗原存在结构上的同源性。该同源性可诱发MS患者自身反应性CD4+/CD8+T细胞活化而导致MS患者免疫损伤,可能是MS的发病机制之一。
Objective To investigate the role of CD4 + / CD8 in patients with multiple sclerosis (MS) who cross-react with human herpesvirus 6 (HHV-6) virus / human herpesvirus 4 (EBV) and myelin basic protein + T cells, as well as the expression of MBP and anti-virus antibodies in serum and cerebrospinal fluid (CSF) of MS patients, and to explore the relationship between MS pathogenesis and HHV-6 / EBV infection. Methods The responses of CD4 + and CD8 + T cells induced by HHV-6 / EBV peptide and MBP peptide in MS patients were analyzed by tritium incorporation of 3H-TdR. High sensitive ELISA kit was used to detect MS The levels of anti-HHV-6 / EBV antibodies in CSF and serum of patients were analyzed. The HLA-DRB1 expression patterns in MS patients were analyzed by primer-specific PCR (SSP-PCR) Results (1) HLA class Ⅱ DRB1 * 04 gene (41.7%) had higher detection rate than healthy control group (18.7%), but the difference was not statistically significant (P> 0.05). (2) High anti-HHV-6 antibodies were detected in the sera of patients with MS, and IgG antibodies against EBV capsid antigen (VCA) IgG and EBV-1 were also detected. (3) The results of 3H-TdR incorporation showed that CD4 + T cells or CD8 + T cells of MS patients both had cross-reactivity to their own MBP peptide and induced HHV-6 / EBV peptide. Conclusion The structural homology of MBP autoantigen between HHV-6 / EBV and MS patients is similar. This homology may induce the activation of autoreactive CD4 + / CD8 + T cells in MS patients, leading to immune damage in MS patients, which may be one of the pathogenesis of MS.